Inhibition of microglial inflammation by the MLK inhibitor CEP-1347


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LUND, Søren, Peter PORZGEN, Anna-Louise MORTENSEN, Henrik HASSELDAM, Donna BOZYCZKO-COYNE, Siegfried MORATH, Thomas HARTUNG, Marina BIANCHI, Pietro GHEZZI, Malika BSIBSI, Sipke DIJKSTRA, Marcel LEIST, 2005. Inhibition of microglial inflammation by the MLK inhibitor CEP-1347. In: Journal of Neurochemistry. 92(6), pp. 1439-1451. ISSN 0022-3042. eISSN 1471-4159

@article{Lund2005Inhib-8000, title={Inhibition of microglial inflammation by the MLK inhibitor CEP-1347}, year={2005}, doi={10.1111/j.1471-4159.2005.03014.x}, number={6}, volume={92}, issn={0022-3042}, journal={Journal of Neurochemistry}, pages={1439--1451}, author={Lund, Søren and Porzgen, Peter and Mortensen, Anna-Louise and Hasseldam, Henrik and Bozyczko-Coyne, Donna and Morath, Siegfried and Hartung, Thomas and Bianchi, Marina and Ghezzi, Pietro and Bsibsi, Malika and Dijkstra, Sipke and Leist, Marcel} }

<rdf:RDF xmlns:rdf="" xmlns:bibo="" xmlns:dc="" xmlns:dcterms="" xmlns:xsd="" > <rdf:Description rdf:about=""> <dc:contributor>Leist, Marcel</dc:contributor> <dc:creator>Bozyczko-Coyne, Donna</dc:creator> <dcterms:title>Inhibition of microglial inflammation by the MLK inhibitor CEP-1347</dcterms:title> <dcterms:bibliographicCitation>First publ. in: Journal of Neurochemistry 92 (2005), 6, pp. 1439-1451</dcterms:bibliographicCitation> <dc:creator>Bianchi, Marina</dc:creator> <dc:creator>Lund, Søren</dc:creator> <dc:date rdf:datatype="">2011-03-24T17:39:11Z</dc:date> <dc:format>application/pdf</dc:format> <dc:creator>Dijkstra, Sipke</dc:creator> <dc:contributor>Ghezzi, Pietro</dc:contributor> <bibo:uri rdf:resource=""/> <dc:contributor>Hasseldam, Henrik</dc:contributor> <dc:creator>Porzgen, Peter</dc:creator> <dc:creator>Leist, Marcel</dc:creator> <dc:contributor>Lund, Søren</dc:contributor> <dc:contributor>Bsibsi, Malika</dc:contributor> <dc:creator>Hasseldam, Henrik</dc:creator> <dc:contributor>Bianchi, Marina</dc:contributor> <dc:contributor>Bozyczko-Coyne, Donna</dc:contributor> <dc:creator>Hartung, Thomas</dc:creator> <dc:contributor>Hartung, Thomas</dc:contributor> <dc:creator>Morath, Siegfried</dc:creator> <dcterms:issued>2005</dcterms:issued> <dcterms:rights rdf:resource=""/> <dc:rights>deposit-license</dc:rights> <dc:creator>Ghezzi, Pietro</dc:creator> <dc:creator>Mortensen, Anna-Louise</dc:creator> <dcterms:abstract xml:lang="eng">CEP-1347 is a potent inhibitor of the mixed lineage kinases (MLKs), a distinct family of mitogen-activated protein kinase kinase kinases (MAPKKK). It blocks the activation of the c-Jun/JNK apoptotic pathway in neurons exposed to various stressors and attenuates neurodegeneration in animal models of Parkinson's disease (PD). Microglial activation may involve kinase pathways controlled by MLKs and might contribute to the pathology of neurodegenerative diseases. Therefore, the possibility that CEP-1347 modulates the microglial inflammatory response [tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemotactic protein-1 (MCP-1)] was explored. Indeed, the MLK inhibitor CEP-1347 reduced cytokine production in primary cultures of human and murine microglia, and in monocyte/macrophage-derived cell lines, stimulated with various endotoxins or the plaque forming peptide Aβ1 40. Moreover, CEP-1347 inhibited brain TNF production induced by intracerebroventricular injection of lipopolysaccharide in mice. As expected from a MLK inhibitor, CEP-1347 acted upstream of p38 and c-Jun activation in microglia by dampening the activity of both pathways. These data imply MLKs as important, yet unrecognized, modulators of microglial inflammation, and demonstrate a novel anti-inflammatory potential of CEP-1347.</dcterms:abstract> <dc:creator>Bsibsi, Malika</dc:creator> <dc:contributor>Mortensen, Anna-Louise</dc:contributor> <dc:contributor>Porzgen, Peter</dc:contributor> <dc:contributor>Dijkstra, Sipke</dc:contributor> <dc:language>eng</dc:language> <dc:contributor>Morath, Siegfried</dc:contributor> <dcterms:available rdf:datatype="">2011-03-24T17:39:11Z</dcterms:available> </rdf:Description> </rdf:RDF>

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